The objective of this research is to study the mechanisms whereby carbamate and organophosphorus insecticides induce acute muscle fiber breakdown. The similarity of the accidentally induced insecticide necrosis in human muscle with that induced experimentally in rat muscle supports the importance of animal studies as a satisfactory model for humans. We will study 1) whether the necrosis is a direct consequence of acetylcholinesterase inhibition and therefore is produced by all anticholinesterases and insecticides, 2) how and when these lesions are repaired, and 3) mechanisms of adaptation. The myopathy producing agents to be studied are carbamates and organophosphorus insecticides. Included in this study are 1) characterization of the morphological and functional changes related to the necrosis; 2) the effect of changes in physiological parameters involved in nerve-muscle activity; 3) the involvement of Ca ions in the development of the necrosis. The methods to be used are 1) histochemical, 2) electrophysiological, 3) biochemical, 4) pharmacological, and 5) electron microscopic.